Adenosine deaminase acting on RNA refers to a family of evolutionarily conserved enzymes known as ADARs that catalyze the conversion of adenosine to inosine within double-stranded regions of cellular RNAs—a process called A-to-I editing. This modification alters base-pairing properties and can recode protein-coding sequences or affect noncoding regulatory elements. In humans there are three main isoforms—ADAR1 (with p110 constitutive and p150 interferon-inducible forms), ADAR2 (constitutively expressed), and catalytically inactive ADAR3—each with distinct tissue distributions and substrate preferences. These enzymes play critical roles across diverse biological processes including nervous system development/functionality, hematopoiesis, innate immunity discrimination between self/non-self nucleic acids via MDA5 pathway modulation, apoptosis regulation through mRNA splicing/translation changes, viral persistence control via viral genome editing/mutation rates modulation—and more recently have been implicated as promising therapeutic targets for cancer immunotherapy as well as genetic/neurodevelopmental/cardiovascular disorders when dysregulated[1][3][4][5].
Other names
Double-stranded RNA-specific adenosine deaminaseAdenosine deaminases acting on RNAADAR1ADAR2ADAR3
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Mechanism of action
Drugs or interventions targeting this molecule would typically act by inhibiting or enhancing its enzymatic activity—specifically the conversion of adenosine to inosine in double-stranded RNAs—or modulating its interaction with other proteins involved in immune signaling or microRNA processing.
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Biological functions
Post-transcriptional gene regulation via A-to-I editing of double-stranded RNAModulation of mRNA translation by altering codonsRegulation of pre-mRNA splicing by changing splice site recognition sequencesControl of innate immune response by marking self vs. non-self dsRNA through inosine formationRegulation of microRNA processing and function
Potential safety concerns include off-target effects leading to widespread changes in transcriptome diversity; disruption may cause severe developmental defects or trigger inappropriate immune activation resulting in autoimmunity—as seen with loss-of-function mutations causing Aicardi–Goutières syndrome. Targeting these enzymes could also impact essential nervous system functions due to their role in neurotransmitter receptor editing.
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Interacting drugs
There are currently no widely approved drugs that directly target ADAR enzymes in clinical use; however, research is ongoing to develop small molecules or oligonucleotide-based therapeutics that modulate their activity for various indications including cancer and genetic disorders. Some experimental compounds have been described in the literature but none are standard therapies yet.
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Biomarkers
Altered levels or patterns of A-to-I editing at specific sites can serve as biomarkers for certain cancers, neurological conditions, autoimmune syndromes such as Aicardi–Goutières syndrome, and possibly cardiovascular risk states.
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